Thomas A. Zeffiro

Meta-Analysis of the Functional Neuroanatomy of Single-Word Reading: Method and Validation

Intersubject variability and subtle differences in experimental design can lead to variable results in studies of cognitive processes such as reading. To accurately identify the neural processes associated with cognition and sensorimotor processing, meta-analytic methods capable of identifying areas of consistent activation among studies are useful. This paper describes a novel approach for combining published neuroimaging results from multiple studies, designed to maximize the quantification of interstudy concordance while minimizing the subjective aspects of meta-analysis. In this method, a localization probability distribution was modeled for each activation focus obtained from 11 PET studies of reading single words aloud, and the union of these distributions was taken to yield an activation likelihood estimate map for the brain. Significance was assessed via permutation analysis of randomly generated sets of foci. Regions of significant concordance were identified in bilateral motor and superior temporal cortices, pre-SMA, left fusiform gyrus, and the cerebellum. These meta-analytic results were validated by comparison with new fMRI data on aloud word reading in normal adult subjects. Excellent correspondence between the two statistical maps was observed, with fMRI maxima lying close to all meta-analysis peaks and statistical values at the peaks identified by the two techniques correlating strongly. This close correspondence between PET meta-analysis and fMRI results also demonstrates the validity of using fMRI for the study of language tasks involving overt speech responses. Advantages of this automated meta-analysis technique include quantification of the level of concordance at all brain locations and the provision for use of a threshold for statistical significance of concordance.

Development of neural mechanisms for reading

The complexities of pediatric brain imaging have precluded studies that trace the neural development of cognitive skills acquired during childhood. Using a task that isolates reading-related brain activity and minimizes confounding performance effects, we carried out a cross-sectional functional magnetic resonance imaging (fMRI) study using subjects whose ages ranged from 6 to 22 years. We found that learning to read is associated with two patterns of change in brain activity: increased activity in left-hemisphere middle temporal and inferior frontal gyri and decreased activity in right inferotemporal cortical areas. Activity in the left-posterior superior temporal sulcus of the youngest readers was associated with the maturation of their phonological processing abilities. These findings inform current reading models and provide strong support for Ortons 1925 theory of reading development.

Neural Changes following Remediation in Adult Developmental Dyslexia

Brain imaging studies have explored the neural mechanisms of recovery in adults following acquired disorders and, more recently, childhood developmental disorders. However, the neural systems underlying adult rehabilitation of neurobiologically based learning disabilities remain unexplored, despite their high incidence. Here we characterize the differences in brain activity during a phonological manipulation task before and after a behavioral intervention in adults with developmental dyslexia. Phonologically targeted training resulted in performance improvements in tutored compared to nontutored dyslexics, and these gains were associated with signal increases in bilateral parietal and right perisylvian cortices. Our findings demonstrate that behavioral changes in tutored dyslexic adults are associated with (1) increased activity in those left-hemisphere regions engaged by normal readers and (2) compensatory activity in the right perisylvian cortex. Hence, behavioral plasticity in adult developmental dyslexia involves two distinct neural mechanisms, each of which has previously been observed either for remediation of developmental or acquired reading disorders.

Functional MRI during word generation, using conventional equipment: A potential tool for language localization in the clinical environment

Objective: To test the accuracy of bilateral language mapping using a standard clinical magnetic resonance (MR) imaging device during word generation. Design. A study of normal volunteers. Setting. Volunteers from the Washington, DC, area. Participants. Nine normal, right-handed, native English speakers (four women, five men, mean age 31 years). Interventions. During four MR acquisition periods, subjects would alternately rest and silently generate words. Sagittal MR images covered the middle and inferior frontal gyri, insulae, and part of the temporal and parietal lobes bilaterally. Main outcome measures. (1) Anatomic maps of task-related signal changes obtained by comparing, in each voxel, the signal during word generation and rest periods, and (2) analysis of the time course of the signal. Results. Maximum responses were in the left hemisphere, mainly in the frontal lobe (Brocas area, premotor cortex, and dorsolateral prefrontal cortex) but also in posterior regions such as Wernickes area. In agreement with previous studies, some degree of task-related changes was present in a subset of the corresponding regions in the right hemisphere. Conclusion. Despite certain limitations, it is possible, using widely available MR equipment, to obtain results consistent with previous studies. The technique may have important implications for assessment of cognitive functions in patients with neurologic disorders in a clinical environment. NEUROLOGY 1995;45: 1821-1827

Categorization Training Results in Shape- and Category-Selective Human Neural Plasticity

Object category learning is a fundamental ability, requiring the combination of bottom-up stimulus-driven with top-down task-specific information. It therefore may be a fruitful domain for study of the general neural mechanisms underlying cortical plasticity. A simple model predicts that category learning involves the formation of a task-independent shape-selective representation that provides input to circuits learning the categorization task, with the computationally appealing prediction of facilitated learning of additional, novel tasks over the same stimuli. Using fMRI rapid-adaptation techniques, we find that categorization training (on morphed cars) induced a significant release from adaptation for small shape changes in lateral occipital cortex irrespective of category membership, compatible with the sharpening of a representation coding for physical appearance. In contrast, an area in lateral prefrontal cortex, selectively activated during categorization, showed sensitivity posttraining to explicit changes in category membership. Further supporting the model, categorization training also improved discrimination performance on the trained stimuli.

Locating the Motor Cortex on the MRI with Transcranial Magnetic Stimulation and PET

Transcranial magnetic stimulation with a focal coil was used to map the cortical representation of a hand muscle in four healthy subjects. In each subject, the three-dimensional locations of the magnetic stimulation positions and about 400 positions on the surface of the head were digitized. The amplitude-weighted center of gravity of each subjects map was found, and a line perpendicular to the local head surface was projected inward. The digitized heads were registered with the subjects MRIs using the scalp contours. The coordinate transformations yielded by this process were used to map the stimulation positions and the perpendicular line into the MRIs. Brain areas imaged with positron emission tomography (PET) and 15O-labeled water, activated by movement of the same muscle, were registered with the MRIs using the brain contours. In all cases, the magnetic stimulation lines encountered the surface of the brain at the anterior lip of the central sulcus and ran along the precentral gyrus a few millimeters anterior to the central sulcus, coming within 5-22 mm of all the PET activation maxima. This technique demonstrates the accuracy of transcranial magnetic stimulation for locating the primary motor area.

Enhanced visual functioning in autism: An ALE meta-analysis

Autistics often exhibit enhanced perceptual abilities when engaged in visual search, visual discrimination, and embedded figure detection. In similar fashion, while performing a range of perceptual or cognitive tasks, autistics display stronger physiological engagement of the visual system than do non‐autistics. To account for these findings, the Enhanced Perceptual Functioning Model proposes that enhanced autistic performance in basic perceptual tasks results from stronger engagement of sensory processing mechanisms, a situation that may facilitate an atypically prominent role for perceptual mechanisms in supporting cognition. Using quantitative meta‐analysis of published functional imaging studies from which Activation Likelihood Estimation maps were computed, we asked whether autism is associated with enhanced task‐related activity for a broad range of visual tasks. To determine whether atypical engagement of visual processing is a general or domain‐specific phenomenon, we examined three different visual processing domains: faces, objects, and words. Overall, we observed more activity in autistics compared to non‐autistics in temporal, occipital, and parietal regions. In contrast, autistics exhibited less activity in frontal cortex. The spatial distribution of the observed differential between‐group patterns varied across processing domains. Autism may be characterized by enhanced functional resource allocation in regions associated with visual processing and expertise. Atypical adult organizational patterns may reflect underlying differences in developmental neural plasticity that can result in aspects of the autistic phenotype, including enhanced visual skills, atypical face processing, and hyperlexia. Hum Brain Mapp, 2011

Altered Processing of Contextual Information during Fear Extinction in PTSD: An fMRI Study

Medial prefrontal cortical areas have been hypothesized to underlie altered contextual processing in posttraumatic stress disorder (PTSD). We investigated brain signaling of contextual information in this disorder. Eighteen PTSD subjects and 16 healthy trauma‐exposed subjects underwent a two‐day fear conditioning and extinction paradigm. On day 1, within visual context A, a conditioned stimulus (CS) was followed 60% of the time by an electric shock (conditioning). The conditioned response was then extinguished (extinction learning) in context B. On day 2, recall of the extinction memory was tested in context B. Skin conductance response (SCR) and functional magnetic resonance imaging (fMRI) data were collected during context presentations. There were no SCR group differences in any context presentation. Concerning fMRI data, during late conditioning, when context A signaled danger, PTSD subjects showed dorsal anterior cingulate cortical (dACC) hyperactivation. During early extinction, when context B had not yet fully acquired signal value for safety, PTSD subjects still showed dACC hyperactivation. During late extinction, when context B had come to signal safety, they showed ventromedial prefrontal cortex (vmPFC) hypoactivation. During early extinction recall, when context B signaled safety, they showed both vmPFC hypoactivation and dACC hyperactivation. These findings suggest that PTSD subjects show alterations in the processing of contextual information related to danger and safety. This impairment is manifest even prior to a physiologically‐measured, cue‐elicited fear response, and characterized by hypoactivation in vmPFC and hyperactivation in dACC.

The role of posterior parietal cortex in visually guided reaching movements in humans.

Abstractu2002Positron emission tomography (PET) was used to identify the brain areas involved in visually guided reaching by measuring regional cerebral blood flow (rCBF) in six normal volunteers while they were fixating centrally and reaching with the left or right arm to targets presented in either the right or the left visual field. The PET images were registered with magnetic resonance images from each subject so that increases in rCBF could be localized with anatomical precision in individual subjects. Increased neural activity was examined in relation to the hand used to reach, irrespective of field of reach (hand effect), and the effects of target field of reach, irrespective of hand used (field effect). A separate analysis on intersubject, averaged PET data was also performed. A comparison of the results of the two analyses showed close correspondence in the areas of activation that were identified. We did not find a strict segregation of regions associated exclusively with either hand or field. Overall, significant rCBF increases in the hand and field conditions occurred bilaterally in the supplementary motor area, premotor cortex, cuneus, lingual gyrus, superior temporal cortex, insular cortex, thalamus, and putamen. Primary motor cortex, postcentral gyrus, and the superior parietal lobule (intraparietal sulcus) showed predominantly a contralateral hand effect, whereas the inferior parietal lobule showed this effect for the left hand only. Greater contralateral responses for the right hand were observed in the secondary motor areas. Only the anterior and posterior cingulate cortices exhibited strong ipsilateral hand effects. Field of reach was more commonly associated with bilateral patterns of activation in the areas with contralateral or ipsilateral hand effects. These results suggest that the visual and motor components of reaching may have a different functional organization and that many brain regions represent both limb of reach and field of reach. However, since posterior parietal cortex is connected with all of these regions, we suggest that it plays a crucial role in the integration of limb and field coordinates.

Neural Systems Affected in Developmental Dyslexia Revealed by Functional Neuroimaging

Table 1Colocalization of Functional Neuroimaging Studies Investigating Differences between Dyslexics and Controls During Phonological and Visual Motion Processing TasksRhyme JudgmentVisual MotionAuthorRumsey et al.Rumsey et al.Rumsey et al.Paulesu et al.Shaywitz et al.Eden et al.Demb et al.(1992)(1997)(1996)(1996)(1998)*(1996)*(1997)*Response typeDecision makingPronunciationDecision makingDecision makingDecision makingNoneNone(button press)(button press)(button press)(button press)#STMRegion (Brodmann area)MTV/V5(19/37) L+50 −70 +05 C--- CR+52 −75 +08 C--- CInferior parietalSupramarginal(39/40) L--- C−28 −32 +44 C−44 −40 +28 C−46 −44 +24 #CR+52 −22 +28 C+40 −62 +28 C+/−47 +/−45 +/−33 CTemporalSuperior temporal(42/22) L−52 −30 +12 C−44 −22 +04 CR+44 −20 −04 C+/−53 +/−43 +/−11 CMedial temporal(21/37) L--- C−54 −22 −04 C−50 −56 +08 CR+46 −58 −08 CInferior temporal/Fusiform L−42 −28 −16 C−48 −40 −16 CR--- C+50 −34 −20 C+48 −30 −20 COccipitalStriate/extrastriate(17/18) L−10 −92 00 D−24 −84 −04 D+/−08 +/−89 +/−03 CR+/−36 +/−80 +/−05 CFunctional brain imaging studies employing PET or fMRI (*) that have identified differences between dyslexics and controls in the posterior areas of the brain during phonological processing or visual motion processing. “C” and “D” denote which of the two groups (controls or dyslexics, respectively) showed greater activation. Talairach coordinates correspond to distance in millimeters from the anterior commissure (+ corresponds to right hemisphere; − corresponds to left hemisphere). Phonological processing studies represent group data and visual motion studies represent single subject data. STM, short-term memory task.